Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged Vs. Immediate Release of Melatonin

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2016 Jan 12

PMID 26751472

Citations 10

Authors

Hui Ming Chua

Nathalie Hauet Richer

Magda Swedrowska

Stephen Ingham

Stephen Tomlin

Ben Forbes

Affiliations

Soon will be listed here.

Abstract

Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

Citing Articles

Development, Characterization, and Evaluation of Potential Systemic Toxicity of a Novel Oral Melatonin Formulation.

Cheaburu-Yilmaz C, Atmaca K, Yilmaz O, Orhan H Pharmaceutics. 2024; 16(7).

PMID: 39065568 PMC: 11279405. DOI: 10.3390/pharmaceutics16070871.

Management of sleep disorders among children and adolescents with neurodevelopmental disorders: A practical guide for clinicians.

Ogundele M, Yemula C World J Clin Pediatr. 2022; 11(3):239-252.

PMID: 35663001 PMC: 9134149. DOI: 10.5409/wjcp.v11.i3.239.

Melatonin for pre-medication in children: a systematic review.

Mellor K, Papaioannou D, Thomason A, Bolt R, Evans C, Wilson M BMC Pediatr. 2022; 22(1):107.

PMID: 35209863 PMC: 8876113. DOI: 10.1186/s12887-022-03149-w.

Concerns regarding tablet splitting: a systematic review.

Saran A, Holden N, Garrison S BJGP Open. 2022; 6(3).

PMID: 35193886 PMC: 9680753. DOI: 10.3399/BJGPO.2022.0001.

Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities.

Talib W, Alsayed A, Abuawad A, Daoud S, Mahmod A Molecules. 2021; 26(9).

PMID: 33923028 PMC: 8123278. DOI: 10.3390/molecules26092506.

References

Cortesi F, Giannotti F, Sebastiani T, Panunzi S, Valente D . Controlled-release melatonin, singly and combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum disorders: a randomized placebo-controlled trial. J Sleep Res. 2012; 21(6):700-9. DOI: 10.1111/j.1365-2869.2012.01021.x. View

Hoebert M, van der Heijden K, van Geijlswijk I, Smits M . Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia. J Pineal Res. 2009; 47(1):1-7. DOI: 10.1111/j.1600-079X.2009.00681.x. View

Brzezinski A, Vangel M, Wurtman R, Norrie G, Zhdanova I, Ben-Shushan A . Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005; 9(1):41-50. DOI: 10.1016/j.smrv.2004.06.004. View

Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C . DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010; 12(3):263-71. PMC: 2895453. DOI: 10.1208/s12248-010-9185-1. View

Carr R, Wasdell M, Hamilton D, Weiss M, Freeman R, Tai J . Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders. J Pineal Res. 2007; 43(4):351-9. DOI: 10.1111/j.1600-079X.2007.00485.x. View

Kennaway D . Potential safety issues in the use of the hormone melatonin in paediatrics. J Paediatr Child Health. 2015; 51(6):584-9. DOI: 10.1111/jpc.12840. View

Braam W, Smits M, Didden R, Korzilius H, van Geijlswijk I, Curfs L . Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis. Dev Med Child Neurol. 2009; 51(5):340-9. DOI: 10.1111/j.1469-8749.2008.03244.x. View

Weiss M, Wasdell M, Bomben M, Rea K, Freeman R . Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry. 2006; 45(5):512-519. DOI: 10.1097/01 chi.0000205706.78818.ef. View

Cardinali D, Pevet P . Basic aspects of melatonin action. Sleep Med Rev. 2004; 2(3):175-90. DOI: 10.1016/s1087-0792(98)90020-x. View

10.

Al-Omary F . Melatonin: comprehensive profile. Profiles Drug Subst Excip Relat Methodol. 2013; 38:159-226. DOI: 10.1016/B978-0-12-407691-4.00005-8. View

11.

Wirojanan J, Jacquemont S, Diaz R, Bacalman S, Anders T, Hagerman R . The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. J Clin Sleep Med. 2009; 5(2):145-50. PMC: 2670334. View

12.

van Someren E . Melatonin treatment efficacy: for whom and for what?. Sleep Med. 2007; 8(3):193-5. DOI: 10.1016/j.sleep.2006.12.008. View

13.

Coppola G, Iervolino G, Mastrosimone M, La Torre G, Ruiu F, Pascotto A . Melatonin in wake-sleep disorders in children, adolescents and young adults with mental retardation with or without epilepsy: a double-blind, cross-over, placebo-controlled trial. Brain Dev. 2004; 26(6):373-6. DOI: 10.1016/S0387-7604(03)00197-9. View

14.

Wright B, Sims D, Smart S, Alwazeer A, Alderson-Day B, Allgar V . Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial. J Autism Dev Disord. 2010; 41(2):175-84. DOI: 10.1007/s10803-010-1036-5. View

15.

Giannotti F, Cortesi F, Cerquiglini A, Bernabei P . An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism. J Autism Dev Disord. 2006; 36(6):741-52. DOI: 10.1007/s10803-006-0116-z. View

16.

Paavonen E, Nieminen-von Wendt T, Vanhala R, Aronen E, von Wendt L . Effectiveness of melatonin in the treatment of sleep disturbances in children with Asperger disorder. J Child Adolesc Psychopharmacol. 2003; 13(1):83-95. DOI: 10.1089/104454603321666225. View

17.

Gordon N . The therapeutics of melatonin: a paediatric perspective. Brain Dev. 2000; 22(4):213-7. DOI: 10.1016/s0387-7604(00)00120-0. View

18.

Ferracioli-Oda E, Qawasmi A, Bloch M . Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013; 8(5):e63773. PMC: 3656905. DOI: 10.1371/journal.pone.0063773. View

19.

Garstang J, Wallis M . Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev. 2006; 32(5):585-9. DOI: 10.1111/j.1365-2214.2006.00616.x. View

20.

de Leersnyder H, Zisapel N, Laudon M . Prolonged-release melatonin for children with neurodevelopmental disorders. Pediatr Neurol. 2011; 45(1):23-6. DOI: 10.1016/j.pediatrneurol.2011.02.001. View